The avidity between immune cells and target cells is crucial for effective immune responses. Here, we present a protocol to measure single-cell avidity between cord blood-derived natural killer (NK) cells and the human acute myelocytic leukemia cell line KG-1a. We describe the steps for isolating cord blood mononuclear cells, purifying NK cells, and culturing KG-1a cells. We then detail the procedures for detecting cell avidity between NK cells and KG-1a cells using the acoustic force-based z-Movi cell avidity analyzer. For complete details on the use and execution of this protocol, please refer to Wang et al..
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http://dx.doi.org/10.1016/j.xpro.2024.103387 | DOI Listing |
Mol Ther Methods Clin Dev
March 2025
Avectas, Cherrywood Business Park, Dublin, Ireland.
Chimeric antigen receptor (CAR)-T cell therapy represents a breakthrough for the treatment of hematological malignancies. However, to treat solid tumors and certain hematologic cancers, next-generation CAR-T cells require further genetic modifications to overcome some of the current limitations. Improving manufacturing processes to preserve cell health and function of edited T cells is equally critical.
View Article and Find Full Text PDFPLoS One
January 2025
Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand.
Anti-programmed cell death 1 (PD-1) monoclonal antibodies (mAbs) have proven to be effective in treating various cancers, including colorectal, lung, and melanoma. Despite their clinical success, some patients develop resistance to mAbs, requiring co-treatments with radio- or chemotherapy. Interleukin-15 (IL-15) is an immunostimulatory cytokine that promotes immune cell production and proliferation.
View Article and Find Full Text PDFNat Immunol
January 2025
Department of Immunology and Neag Comprehensive Cancer Center, University of Connecticut School of Medicine, Farmington, CT, USA.
T cells recognize neoepitope peptide-major histocompatibility complex class I on cancer cells. The strength (or avidity) of the T cell receptor-peptide-major histocompatibility complex class I interaction is a critical variable in immune control of cancers. Here, we analyze neoepitope-specific CD8 cells of distinct avidities and show that low-avidity T cells are the sole mediators of cancer control in mice and are solely responsive to checkpoint blockade in mice and humans.
View Article and Find Full Text PDFFront Immunol
January 2025
Molecular Immunology and Gene Therapy, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.
View Article and Find Full Text PDFMHC-I proteins present epitopic peptides to CD8+ T cells to elicit multifaceted adaptive immune responses. The affinity and avidity of interactions between peptide-MHC molecules and T-cell receptors (TCR) are fundamental parameters that contribute to the induction of activated or anergic T cell states. Here, we present a loadable system, VLP-Open HLA, featuring a virus-like particle (VLP) that can accommodate up to 60 loadable HLA (HLA - human leukocyte antigen) molecules.
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